The tumour-suppressive function of miR-1 and miR-133a targeting TAGLN2 in bladder cancer
Open Access
- 8 February 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 104 (5), 808-818
- https://doi.org/10.1038/bjc.2011.23
Abstract
On the base of the microRNA (miRNA) expression signature of bladder cancer (BC), we found that miR-1 and miR-133a were significantly downregulated in BC. In this study, we focussed on the functional significance of miR-1 and miR-133a in BC cell lines and identified a molecular network of these miRNAs. We investigated the miRNA expression signature of BC clinical specimens and identified several downregulated miRNAs (miR-133a, miR-204, miR-1, miR-139-5p, and miR-370). MiR-1 and miR-133a showed potential role of tumour suppressors by functional analyses of BC cells such as cell proliferation, apoptosis, migration, and invasion assays. Molecular target searches of these miRNAs showed that transgelin 2 (TAGLN2) was directly regulated by both miR-1 and miR-133a. Silencing of TAGLN2 study demonstrated significant inhibitions of cell proliferation and increase of apoptosis in BC cell lines. The immunohistochemistry showed a positive correlation between TAGLN2 expression and tumour grade in clinical BC specimens. The downregulation of miR-1 and miR-133a was a frequent event in BC, and these miRNAs were recognised as tumour suppressive. TAGLN2 may be a target of both miRNAs and had a potential oncogenic function. Therefore, novel molecular networks provided by miRNAs may provide new insights into the underlying molecular mechanisms of BC.Keywords
This publication has 40 references indexed in Scilit:
- Genetic variation in microRNA networks: the implications for cancer researchNature Reviews Cancer, 2010
- MicroRNA Cluster 221-222 and Estrogen Receptor α Interactions in Breast CancerJNCI Journal of the National Cancer Institute, 2010
- miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancerBritish Journal of Cancer, 2010
- Tissue Proteomics Reveals Differential and Compartment-Specific Expression of the Homologs Transgelin and Transgelin-2 in Lung Adenocarcinoma and Its StromaJournal of Proteome Research, 2009
- MicroRNA-1/206 Targets c-Met and Inhibits Rhabdomyosarcoma DevelopmentJournal of Biological Chemistry, 2009
- MicroRNA control of muscle development and diseaseCurrent Opinion in Cell Biology, 2009
- Down-regulation of Micro-RNA-1 (miR-1) in Lung Cancer: Suppression of Tumorigenic Property of Lung Cancer Cells and Their Sensitization to Doxorubicin-Induced Apoptosis by miR-1Journal of Biological Chemistry, 2008
- Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight?Nature Reviews Genetics, 2008
- MicroRNA Signatures in Human CancersNature Reviews Cancer, 2006
- MicroRNA expression profiles classify human cancersNature, 2005